Empirical rules for rationalising visible circular dichroism of Cu super(2) super(+) and Ni super(2) super(+) histidine complexes: Applications to the prion protein

• Published in: FEBS letters Vol. 581; no. 7; pp. 1430 - 1434
• Main Authors: Klewpatinond, M, Viles, J H
• Format: Journal Article
• Language: English
• Published: 03-04-2007
• ISSN: 0014-5793
• DOI: 10.1016/j.febslet.2007.02.068

A natively unfolded region of the prion protein, PrP(90-126) binds Cu super(2) super(+) ions and is vital for prion propagation. Pentapeptides, acyl-GGGTH super(9) super(2) super(-) super(9) super(6) and acyl-TNMKH super(1) super(0) super(7) super(-) super(1) super(1) super(1), represent the minimum motif for this Cu super(2) super(+) binding region. EPR and super(1)H NMR suggests that the coordination geometry for the two binding sites is very similar. However, the visible CD spectra of the two sites are very different, producing almost mirror image spectra. We have used a series of analogues of the pentapeptides containing His super(9) super(6) and His super(1) super(1) super(1) to rationalise these differences in the visible CD spectra. Using simple histidine-containing tri-peptides we have formulated a set of empirical rules that can predict the appearance of Cu super(2) super(+) visible CD spectra involving histidine and amide main-chain coordination.